A novel mutation in DAX1 (NR0B1) causing X-linked adrenal hypoplasia congenita: clinical, hormonal and genetic analysis.

The association of primary adrenal insufficiency and hypogonadotropic hypogonadism is extremely infrequent in daily clinical practice. Differential diagnosis includes X-linked adrenal hypoplasia congenita, a genetic disease characterized by an alteration in the formation of the adrenal glands and the hypothalamus-pituitary-gonadal axis. The gene responsible is DAX1 (NR0B1). The most common form of clinical presentation is neonatal primary adrenal insufficiency and complete hypogonadotropic hypogonadism. Members of a single family often present the same clinical form, although there may be relatives affected with different clinical symptoms. The aim of this study is to characterize clinically and genetically a family affected by different forms of hypogonadotropic hypogonadism and/or primary adrenal insufficiency. We describe a family with three members affected, two adults and a neonate. The way of presentation of the adults was neonatal primary adrenal insufficiency and hypogonadotropic hypogonadism (one complete and another presenting as interrupted puberty). The genetic study revealed a new mutation in DAX1, p.Q76X gene (c.C226T), resulting in a truncated protein of 76 amino acids, the same in all three affected male patients and in the asymptomatic women of the family. These cases further expand the number of DAX1 mutations reported, as well as the description of infrequent forms of presentation of this disease as interrupted puberty.